Pathologies liées aux déficits du cycle de Krebs

Published on Apr 1, 2018in Revue Francophone Des Laboratoires
· DOI :10.1016/s1773-035x(18)30120-5
Paule Bénit29
Estimated H-index: 29
(French Institute of Health and Medical Research),
Sylvie Bortoli8
Estimated H-index: 8
(Paris V: Paris Descartes University)
+ 2 AuthorsPierre Rustin80
Estimated H-index: 80
(French Institute of Health and Medical Research)
Resume Chez l'homme, les dysfonctions des enzymes du cycle de Krebs liees a des mutations causent des encephalopathies severes du jeune enfant, ou differents types de tumeurs et de cancers touchant differents organes. Ainsi des mutations des genes de la succinate-deshydrogenase ont ete identifiees dans des formes familiales de pheochromocytomes et paragangliomes. Les mutations du gene de la fumarase s'observent dans des leiomyomes uterins en association avec des cancers renaux, mais des cas d'encephalopathies de l'enfant ont aussi ete observes. Les mutations des genes de l'isocitrate-deshydrogenase peuvent representer jusqu'a 20% des leucemies myeloides aigues et jusqu'a 80% dans certains gliomes. On ne sait actuellement expliciter la diversite des consequences possibles de ces mutations : encephalopathies versus cancers, nature des tissus affectes, cinetique variable d'apparition des symptomes. Il semble en revanche etabli que les anomalies dans les equilibres metaboliques qui resultent de ces mutations soient a la base des processus tumoraux en modulant l'activite d'hydroxylases susceptibles d'affecter certains facteurs de transcriptions, mais aussi la methylation de l'ADN et les histones. Dans ce contexte, il semble etonnant que soient largement utilises certains fongicides dont l'effet est de bloquer une etape centrale du cycle de Krebs, la succinate-deshydrogenase. Le principe de precaution voudrait sans aucun doute de reevaluer urgemment la necessite de l'usage de telles substances pour l'homme et l'environnement.
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